Your Genetic CAG Repeat Number Determines How Well You Will Respond to Testosterone

Nelson Vergel · Oct 25, 2015

Androgen Receptor Gene CAG Repeat Polymorphism Independently Influences Recovery of Male Sexual Function After Testosterone Replacement Therapy in Postsurgical Hypogonadotropic Hypogonadism

Tirabassi G, delli Muti N, Corona G, Maggi M, Balercia G. Androgen Receptor Gene CAG Repeat Polymorphism Independently Influences Recovery of Male Sexual Function After Testosterone Replacement Therapy in Postsurgical Hypogonadotropic Hypogonadism. The Journal of Sexual Medicine. http://onlinelibrary.wiley.com/doi/10.1111/jsm.12493/abstract

Introduction Few and contradictory studies have evaluated the possible influence of androgen receptor (AR) gene CAG repeat polymorphism on male sexual function.

Aim In this study we evaluated the role of AR gene CAG repeat polymorphism in the recovery of sexual function after testosterone replacement therapy (TRT) in men affected by postsurgical hypogonadotropic hypogonadism, a condition which is often associated with hypopituitarism and in which the sexual benefits of TRT must be distinguished from those of pituitary-function replacement therapies.

Methods Fifteen men affected by postsurgical hypogonadotropic hypogonadism were retrospectively assessed before and after TRT.

Main Outcome Measures Main outcome measures included sexual parameters as assessed by the International Index of Erectile Function questionnaire, levels of pituitary dependent hormones (total testosterone, free T3, free T4, cortisol, insulin-like growth factor-1 [IGF-1], prolactin), and results of genetic analysis (AR gene CAG repeat number).

Results Plasma concentrations of free T3, free T4, cortisol, and prolactin did not vary significantly between the two phases, while testosterone and IGF-1 increased significantly after TRT. A significant improvement in all sexual parameters studied was found.

The number of CAG triplets was negatively and significantly correlated with changes in all the sexual parameters, while opposite correlations were found between changes in sexual parameters and changes in testosterone levels; no correlation of change in IGF1 with change in sexual parameters was reported.

On multiple linear regression analysis, after correction for changes in testosterone, nearly all the associations between the number of CAG triplets and changes in sexual parameters were confirmed.

Conclusions Shorter length AR gene CAG repeat number is associated with the recovery of sexual function after TRT in postsurgical male hypogonadotropic hypogonadism, independently of the effects of concomitant pituitary-replacement therapies.

Nelson Vergel · Oct 25, 2015

Genes are made up of the genetic material called DNA. DNA is the code for all life and is made up of a combination of 4 ‘letters' - A, C, G and T. Scientifically, these genetic letters are called ‘nucleotide bases'.

DNA is a polymer. The monomer units of DNA are nucleotides, and the polymer is known as a "polynucleotide." Each nucleotide consists of a 5-carbon sugar (deoxyribose), a nitrogen containing base attached to the sugar, and a phosphate group. There are four different types of nucleotides found in DNA, differing only in the nitrogenous base. The four nucleotides are given one letter abbreviations as shorthand for the four bases.
A is for adenine
G is for guanine
C is for cytosine
T is for thymine

How many times the C-A-G repeats seems to affect response to testosterone replacement.

ERO · Oct 26, 2015

This is very, very interesting. Great info Nelson! As I seem to barely respond at all to Testosterone - I have been on TRT for 5 years, and find it hard to tell the difference between 'on' and 'off' at any measure, sexual, [lack of] muscle building or fat loss, even with total T over 1000 and E2 in the sweet spot - this potentially explains a lot.

HarryCat · Oct 26, 2015

Yes, this is very interesting. I wonder if 23andMe testing can figure out if someone has this mutation. I tried looking up what 23andMe tests for and couldn't find anything.

Nelson Vergel · Oct 26, 2015

You could email the investigators.They are in Italy, though.

Corresponding Author: Giancarlo Balercia, MD, Andrology Unit, Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Via Conca 71, Ancona 60126, Italy. Tel: +39 071-596-3738; Fax: +39 071-887-300; E-mail:[email protected]; [email protected]

HarryCat · Oct 26, 2015

Here is another similar study by the same group:

Influence of Androgen Receptor CAG Polymorphism on Sexual Function Recovery after Testosterone Therapy in Late-Onset Hypogonadism

Abstract

Introduction

Androgen receptor (AR) CAG polymorphism has been found to influence sexual function. However, no study has evaluated its potential to condition sexual function recovery after testosterone replacement therapy (TRT) in a large cohort of hypogonadic subjects.

Aim

To evaluate the role of this polymorphism in sexual function improvement after TRT in late-onset hypogonadism (LOH).

Methods

Seventy-three men affected by LOH were retrospectively considered. Evaluations were performed before TRT started (time 0) and before the sixth undecanoate testosterone injection.

Main Outcome Measures

International Index of Erectile Function (IIEF) questionnaire (erectile function [EF], orgasmic function [OF], sexual desire [SD], intercourse satisfaction [IS], overall satisfaction [OS], and total IIEF-15 score); total and free testosterone and estradiol; AR gene CAG repeat number.

Results

TRT induced a significant increase in total and free testosterone and estradiol. All IIEF domains significantly improved after TRT. AR CAG repeats negatively and significantly correlated with all the variations (Δ-) of sexual function domains, except for Δ-OS. Conversely, Δ-total testosterone was found to be positively and significantly correlated with sexual function domain variations, except for Δ-IS and Δ-OS. Δ-estradiol did not correlate significantly with any of the variations of sexual function domains. After inclusion in generalized linear models, the number of AR gene CAG triplets was found to be independently and negatively associated with Δ-EF, Δ-SD, Δ-IS, and Δ-Total IIEF-15 score, whereas Δ-total testosterone was independently and positively associated with Δ-EF, Δ-OF, Δ-SD, and Δ-Total IIEF-15 score. However, after including time 0 total testosterone in the model, AR gene CAG triplets remained independently and negatively associated only with Δ-EF and Δ-Total IIEF-15 score, whereas Δ-total testosterone was independently and positively associated only with Δ-EF.

Conclusions

Longer length of AR gene CAG repeat tract seems to lower TRT-induced improvement of sexual function in LOH. Tirabassi G, Corona G, Biagioli A, Buldreghini E, delli Muti N, Maggi M, and Balercia G. Influence of androgen receptor CAG polymorphism on sexual function recovery after testosterone therapy in late-onset hypogonadism. J Sex Med 2015;12:381–388.